IgA nephropathy (IgAN), also called Berger disease, was described in 1968 based on the immunohistochemical finding of IgA- and IgG-containing immune complexes in the glomerular mesangium of the kidney. Proliferation of mesangial cells and expansion of the extracellular matrix can occur from the earliest stages of the disease, with progression to glomerular and interstitial sclerosis resulting in development of end-stage renal disease in 30%-40% of patients within 20 years of the estimated time of disease onset.
The IgA in the mesangial deposits is exclusively of the IgA1 subclass and is aberrantly glycosylated, with the hinge-region O-linked glycans being deficient in galactose (Gal). The IgA1 in the circulation of patients with IgAN also carries Gal-deficient O-glycans, although Gal-deficient variants are rarely found in the IgA1 in sera from normal individuals. The production of these variants is associated with altered expression of specific glycosyltransferases in the IgA1-producing cells. It is the binding of IgA1-containing immune complexes with aberrantly glycosylated IgA1 to mesangial cells that induces the renal manifestations characteristic of IgAN; however, the events that initiate the disease process are most likely of extra-renal origin, as IgAN recurs in more than 50% of patients within 2 years of kidney transplantation.